title: Selective increases of extracellular brain concentrations of aromatic and branched-chain amino acids in relation to deterioration of neurological status in acute (ischemic) liver failure.
abstract: Previous reports based on studies in brain tissue from humans and experimental animals suggest that aromatic amino acids (AAAs) and branched-chain amino acids (BCAA's) accumulate in brain in acute liver failure. In order to assess these changes in relation to the severity of neurological impairment and to the degree of hyperammonemia, AAAs and BCAAs were measured in vivo by cerebral microdialysis in frontal cortex of rats at various stages during the development of hepatic encephalopathy due to acute liver failure resulting from portacaval anastomosis followed by hepatic artery ligation. Extracellular brain concentrations of AAAs and of valine and leucine were elevated 2 to 4-fold following hepatic devascularization and these increases were significantly correlated to arterial ammonia concentration (r= 0.71-0.84, p<0.05). Extracellular concentrations of tyrosine paralleled the deterioration of neurological status in acute liver failure rats. In view of their role as precursors of monoamine neurotransmitters, ammonia-induced alterations of intracellular/extracellular brain concentration ratios for AAAs could account for altered neuronal excitability and contribute to the encephalopathy characteristic of acute liver failure.
authors.affiliation: Neuroscience Research Unit, Pavillon Saint-Luc (University of Montreal), Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Michalak
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis*; D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain